The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art.
Many chronic pathological conditions associated with mitochondrial dysfunction such as metabolic syndrome, diabetes, neurodegenerative diseases, and atherosclerosis are associated with an inflammatory response with the release of proinflammatory mediators, particularly cytokines. Monocytes are phagocytic cells that play an important role in the innate immune system. Once secreted from the bone marrow into the blood, these cells survey the body for sites of inflammation. On encountering inflammatory stress signals the monocytes must rapidly activate and migrate to areas of injury where they can differentiate into the pro-inflammatory “killer” (M1) or anti-inflammatory “repair” (M2) phenotype. Both human classical and intermediate monocytes have inflammatory properties that are reminiscent of M1 phenotype, while non-classical monocytes display properties similar to M2 phenotype.
In the M1 state, the activated monocyte-macrophage cell undergoes a metabolic switch from oxidative phosphorylation to glycolysis. This switch is important because it provides substrates for biosynthetic programs, maintains mitochondrial membrane potential and results in ATP production within the cell. Inhibition of oxidative phosphorylation also increases reactive oxygen species (ROS) production which exerts bactericidal activities. During the resolution of inflammation, the macrophages transform into the alternatively activated M2 phenotype and a more oxidative phosphorylation phenotype. Thus, the metabolic programs of monocyte/macrophage populations are highly plastic and adapt to facilitate the changing function of these cells in the inflammatory process. Currently, it is unclear whether early changes in metabolic phenotype associated with exposure to pro-inflammatory conditions can be detected in the pre-differentiated circulating monocytes.